Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM1ATVR)

• DOT Name: Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase (ALG10)
• Synonyms: EC 2.4.1.256; Alpha-1,2-glucosyltransferase ALG10-A; Alpha-2-glucosyltransferase ALG10-A; Asparagine-linked glycosylation protein 10 homolog A
• Gene Name: ALG10
• Related Disease:
  Hepatitis C virus infection
  Long QT syndrome
  Ventricular fibrillation
  Arrhythmia
• UniProt ID: AG10A_HUMAN
• EC Number: 2.4.1.256
• Pfam ID: PF04922
• Sequence:
  MAQLEGYYFSAALSCTFLVSCLLFSAFSRALREPYMDEIFHLPQAQRYCEGHFSLSQWDP
  MITTLPGLYLVSIGVIKPAIWIFGWSEHVVCSIGMLRFVNLLFSVGNFYLLYLLFCKVQP
  RNKAASSIQRVLSTLTLAVFPTLYFFNFLYYTEAGSMFFTLFAYLMCLYGNHKTSAFLGF
  CGFMFRQTNIIWAVFCAGNVIAQKLTEAWKTELQKKEDRLPPIKGPFAEFRKILQFLLAY
  SMSFKNLSMLLLLTWPYILLGFLFCAFVVVNGGIVIGDRSSHEACLHFPQLFYFFSFTLF
  FSFPHLLSPSKIKTFLSLVWKRRILFFVVTLVSVFLVWKFTYAHKYLLADNRHYTFYVWK
  RVFQRYETVKYLLVPAYIFAGWSIADSLKSKSIFWNLMFFICLFTVIVPQKLLEFRYFIL
  PYVIYRLNIPLPPTSRLICELSCYAVVNFITFFIFLNKTFQWPNSQDIQRFMW
• Function: Adds the third glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Glc(2)Man(9)GlcNAc(2)-PP-Dol.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein (R-HSA-446193)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[1]
Long QT syndrome	DISMKWS3	moderate	Genetic Variation	[2]
Ventricular fibrillation	DIS7IN76	moderate	Genetic Variation	[2]
Arrhythmia	DISFF2NI	Limited	Altered Expression	[3]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase (ALG10).	[4]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase (ALG10).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase (ALG10).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase (ALG10).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase (ALG10).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase (ALG10).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase (ALG10).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase (ALG10).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase (ALG10).	[12]

References

• [1] A genetic screen identifies interferon- effector genes required to suppress hepatitis C virus replication.Gastroenterology. 2013 Jun;144(7):1438-49, 1449.e1-9. doi: 10.1053/j.gastro.2013.02.026. Epub 2013 Feb 24.
• [2] A KCR1 variant implicated in susceptibility to the long QT syndrome.J Mol Cell Cardiol. 2011 Jan;50(1):50-7. doi: 10.1016/j.yjmcc.2010.10.007. Epub 2010 Oct 13.
• [3] HERG is protected from pharmacological block by alpha-1,2-glucosyltransferase function.J Biol Chem. 2007 Feb 23;282(8):5506-13. doi: 10.1074/jbc.M605976200. Epub 2006 Dec 21.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.